1. INTRODUCTION:

Viral diseases like Influenza, COVID-19, Ebola, SARS, CCHF, Marburg virus disease, Nipah. Virus, are potential risk for public health. One of the most lethal viruses in the world, the Nipah virus (NiV) belongs to the family paramyxovirdae of the Henipavirus genus.

In 1998/99, a pig encephalitis epidemic in Malaysia led to the discovery of NiV^1,2,3. It was originally thought to be the source of epidemics of febrile respiratory infections in livestock. Viruses that may transcend species boundaries to infect humans, other domestic animals, and wild mammals can be found in certain bat species⁴, about 1 million pigs were slaughtered, which helped contain the spread but had a substantial financial cost⁴. Since then, there have been numerous epidemics of NiV in Bangladesh and India^5,6,7,8,9,10. NiV Malaysia (NiV-M) and NiV Bangladesh (NiV-B) are two genetically different strains of NiV. Currently, only NiV-B is being spread¹¹. Treatment relies mostly on supportive care, such as maintaining airways, breathing, and circulation as well as ensuring fluid and electrolyte balance. There have been several human-to-human transmissions connected with overflow episodes from the natural fruit bat reservoir host^12,13. A vaccine and therapies for NiV are needed because of the virus severe pathogenicity and pandemic potential, as well as its possible use in (agro) bioterrorism¹⁴.

2. METHODOLOGY:

We used PubMed and Google Scholar to perform a literature search on NIV. A number of MeSH words were utilized, including: ‘Epidemiology Nipah Virus’, ‘Pathogenicity Nipah virus’, ‘Surveillance Nipah virus’, ‘Nipah virus Bangladesh’, Nipah virus infection India’, ‘Nipah virus Malaysia’, ‘Nipah virus Philippines’, Nipah virus Singapore’. The scope of the search was narrowed to include only items that were published between January 1, 1998 and May 1, 2022. After each author had independently read through the papers, they came together to discuss what they had found. The objective of this search technique was to locate published material that provided an explanation of how the illness is spread, the demographics of the Nipah Virus outbreak, and the molecular behavior of NIV.

3. PATHOGENICITY OF NIPAH VIRUS IN DIFFERENT ANIMALS:

3.1 Human:

The Nipah virus causes fever, mental decline, coma, and death¹⁵. Pulmonary sickness may arise with Nipah virus infection. In 1998-1999, almost half of the Bangladeshi cases had respiratory problems, although only 25% of Malaysian and Singaporean cases did¹⁶. Radiographs of Bangladeshi patients showed significant respiratory distress. In Malaysia and Singapore, the Nipah virus's case-fatality ratio was 30–40%; in Bangladesh and India¹⁷, it was 70–100%, although it reached 100% in some outbreaks. Nipah virus survivors often have neurological issues¹⁸. Late-onset or relapses after the original Nipah virus infection have been reported¹⁹, including one over 11 years later¹⁹. The only investigation on histopathological alterations in Nipah virus-infected patients was conducted during the epidemic in Malaysia and Singapore²⁰. The Nipah virus infection most impacted the endothelium. Systemic vasculitis afflicts all patients, mainly the CNS and the respiratory, cardiac, and renal blood vessels²¹. The artery region showed necrosis, cell death, and endothelial cell syntactic. Immunohistochemistry showed Nipah-infected central nervous system neurons²². Alveoli surrounding vasculitis-infected microcapillaries showed fibrinoid necrosis. Patients had lung edema and alveolar bleeding. Patients' spleens had swollen lymph nodes and necrotizing periarteriolar sheaths. Symptomatic glomerular fibrinoid necrosis affected 30% of kidneys²³.

Figure 1: Viral Replication of NIV in human body²⁴

3.2 Syrian hamsters:

Toxic respiratory and neurological disorders were found after the Nipah virus was administered to Syrian hamsters, which developed at higher and lower levels of inoculum²⁵. When compared to intranasal injection, intraperitoneal inoculation has been proven to have a greater influence on the spread of the disease and the time it takes to die. Animals and humans alike were affected by this phenomenon²⁶. Syrian hamsters inoculated with the Nipah virus showed signs of systemic vasculitis similar to those seen in humans. In addition, the animals experienced encephalitis, and it was clear that the neurons in the brain and spinal cord had been infected with the bacteria that caused the disease²⁷. Nucleoprotein aggregates in inclusion bodies were discovered utilizing electron microscopy and immunohistochemistry as a means of identifying the virus antigen. Rhinitis was seen in hamsters with severe respiratory illness following olfactory treatment²⁸. The virus propagated in the animals' respiratory and olfactory epithelia. Animals got broncho-interstitial pneumonia in their lungs^29,30.

3.3 Ferrets:

Nipah-infected animals developed respiratory and neurological issues³¹. Virus-infected ferrets developed vasculitis. The investigation identified necrotizing broncho-interstitial pneumonia in the lower respiratory tract, sneezing, sinusitis, and swollen glands in the upper respiratory tract³². Viral antigen was found in certain animals' endothelium, cerebrospinal meningitis, and nearby neurons. Encephalitis was absent³³.

3.4 African Green Monkeys:

Infected African green monkeys developed ARDS³⁴. Nipah virus antigen was discovered in all animals lungs and neurons; histology revealed systemic vasculitis³⁵.

3.5 Cats:

Subcutaneous, intranasal, or oral administration of the Nipah virus inoculated cats showed signs of respiratory disease³⁶. The cats exhibited broncho-interstitial pneumonia and meningitis, according to histopathological investigation^37,38.

3.6 Mice

Nipah virus does not cause illness in conventional laboratory mice strains like Balb/c and C57BL/6 when administered intraperitoneally or intranasally³⁹. The intracerebral injection of the pathogen, however, resulted in a lethal infection in these animals. When administered intravenously to aged mice, the NIPAH virus did not cause any clinical symptoms or seroconversion or infectious virus to be detected in the lung tissue until 2 to 15 days after the initial inoculation⁴⁰. In IFNAR-KO mice lacking the type I interferon receptor, intraperitoneal injection resulted to neurological disease⁴¹. Animals with vasculitis and meningeal irritation were found on histological examination. Broncho-interstitial pneumonia was also seen in the lungs⁴².

3.7 Horses:

Immunohistochemical detection of viral antigen in a naturally infected horse's brain and spinal cord revealed that the horse had non-suppurative meningitis. Natural infection of horses with NiV has been recorded despite no attempts at experimental NiV infection of horses⁴³.

4. Mechanisms behind the Spread of the Nipah Virus:

According to research conducted using hamsters infected with HeV⁴⁴, the virus is more likely to be spread via personal contact than by inhalation of infectious droplets⁴⁵. The HeV and the NiV-Malaysia strains have different starting replication sites, which may explain why the zoonotic transmission efficiency of both strains was discovered during epidemics⁴⁶. A ferret model can be used to better understand the spread of NiV in Bangladesh. NiV-Bangladesh is present in an individual's oral secretions in greater quantities than NiV-Malaysia, according to the findings of the model. This explains why there have been more cases of the transmission of NiV amongst people in Bangladesh⁴⁷.

Figure 1: Binding the site of NIV at neuron by Ephrin B2/B3⁴⁶.

4.1 Routes of Fruit Bat-to-Human and Human-to-Human:

In Bangladesh, the most frequent way to get the disease is by the eating of raw date palm sap that has been contaminated with the urine or saliva of fruit bats⁴⁸. This is particularly prevalent in Western Bangladesh. People have the tradition of gathering fresh date palm juice in order to prepare tari, which is part of the local rituals. The members of the community recycle the clay jars without first cleaning them. Those that have been digested by fruit bats poison the clay jars and the subsequent tari, which infects the subsequent customer who purchases tari⁴⁹. More than half of the cases of NiV infection in Bangladesh between the years 2001 and 2012 were caused by drinking fresh date palm juice⁵⁰, according to the statistics found in the related literature. This is despite the fact that there were multiple causes of NiV infection during this time period. In 1999, individuals suffering from encephalitis like Nipah were the first to have the virus identified. There were several individuals here who suffered from respiratory conditions⁵¹. In 2001, India revealed that NiV may be transferred to the relatives of patients as well as medical workers via the droplets and saliva of patients who had the virus⁵². In Bangladesh, family members of patients, as well as medical professionals, have been infected due to the fact that physicians do not use gloves and masks while checking on patients, and family members of patients do not take the necessary precautions to protect themselves when they visit patients⁵³. In addition to this, the risk of contracting an infection when providing treatment to patients with NiV is significantly raised⁵⁴. Additionally, in Bangladesh, in line with the local traditions, the relatives of the patients perform a ritual during the burial of the dead in which they kiss the corpse and wipe the bodily fluids of the deceased. This is done in order to show respect for the departed. On the other side, after the ritual, they often do not wash their hands⁵⁵. Therefore, the risk of infection is increased while engaging in this form of interaction without taking any preventative steps⁵⁶.

4.2 Transmission of Fruit Bat Virus to Livestock and Ultimately to Humans through Fruit Bats:

If livestock consume wild fruits that bats have contaminated with the NiV virus, there is a risk that the animals will contract the virus and become affected themselves. After becoming infected themselves, animals have the potential to transfer the virus on to other species, including humans. Pigs can contract NiV if they consume infected fruit buds or fruits that have been contaminated by saliva that has come into contact with the fruit. In 2014, the Philippines were the location of a NiV incident that was recorded. There is a good chance that the Nipah virus was the cause of the outbreak that took place in the Philippines. As a result of this particular incidence, there were 17 people who were ill, and nine of them ultimately went away, which results in a mortality rate of 53 percent⁵⁷. Even though it was uncertain how the horses became infected with the NiV virus, fruit bats were discovered in the area that was ravaged by the pandemic. This was the case despite the fact that the bats were located in the region. There is a hypothesis that the illness was caused by the horses swallowing feed that had been contaminated by the urine and feces of fruit bats, and this hypothesis has gained some traction⁵⁸.

4.3 Route of Fruit bats to humans:

In total, there are 188 species of bats, divided into 42 distinct genera. There are 59 species of fruit bats in the Pteropodidae family⁵⁹. Among the fruit bats' most popular swarming grounds are South Asia, Southeast Asia, Australia, and the African Continent. A virus that was found in the serum of some Cameroonian residents was found to be extremely similar to the Henipavirus⁶⁰. Most of those who were affected were thought to have been involved in the hunting and killing of local bats, which is largely accepted. A virus closely related to henipaviruses is thought to be circulating in this area since serum reacts with both NiV and HeV⁶¹. Cambodian Pteropus lylei had antibodies to a NiV-like virus, even though Nipah-positive antibodies were not found in Cambodian individuals. Bat slaughtering is another activity that exposes residents to the risk of NiV infection in the area⁶².

5. Demographic Outbreak of Nipah Virus:

The human henipah virus was poorly understood prior to an outbreak in Malaysia in 1999⁶³. In the wake of the Nipah outbreak in Malaysia, the global public health community has taken notice of the unique paramyxoviruses pathogenic potential and vast dissemination. Nipah virus detection and an initial diagnosis of the etiological agent responsible for fever encephalitis are briefly discussed in this chapter, which outlines some of the difficulties encountered⁶⁴. There have also been reports of early attempts to isolate the Nipah virus from the bat's reservoir host. The Nipah virus was initially discovered in 1998 in the Malaysian town of Kampung Sungai Nippon. Other countries of the South and Southeast Asia have seen outbreaks of the disease. It can lead to life-threatening neurological and pulmonary complications⁶⁵. This extremely contagious virus spreads by contact with infected animals or other affected individuals in the community⁶⁶. For the first time, the nipah virus outbreak in Malaysia causes 265 cases of acute encephalitis and 105 deaths. As a result of this, it has been linked to a high mortality rate in the human population⁶⁵. Henipavirus genus Henipavirus of family Paramyxoviridae includes NiV and Hendra virus. In reality, fruit bats (genus Pteropus) are the true hosts and reservoirs of the NiV pathogen⁶⁷.

In the case of epidemics in Malaysia and Singapore, pigs serve as an intermediate hosts. There is a required method of transmission of NiV from bats to humans via pigs and, subsequently, humans. Human-to-human transmission is another mode of communication. The half-life of NiV in bat pee is approximately 18 hours⁶⁸. Methods for the spread of the Nipah Virus occur in three ways: through the ingestion of contaminated food, the contact with infected bodily fluids (human or animal), and the inhalation of aerosols or drops. Close contact with an infected person is one of the risk factors for infection. Dates and fruits infected foods include palm sap contaminated with bat body secretions⁶⁹.

6. Outbreaks of Nipah Virus in Different Countries:

6.1 Malaysia:

Since NiV was discovered in a patient's cerebrospinal fluid (CSF) in March 1999, it has been known as the Sungai Nipah Virus⁷⁰. Another outbreak occurred in Singapore in 1999, with 11 illnesses and one death. There have been hundreds of human deaths due to sporadic outbreaks and person-to-person transmission over the last two decades⁷¹. This study looked at NiV serosurveillance in Peninsular Malaysia, particularly among indigenous people. In an indirect comparative enzyme-linked immunosorbent test⁷², the recombinant NiV nucleocapsid (rNiV-N) protein was utilized to assess for NiV antibodies in the collected samples. NiV-N antibodies were found in 10.73 percent of the patients in this study, which implies possible exposure to the virus⁷³.

6.2 Bangladesh:

The outbreak of encephalitis in Meherpur, Bangladesh, began in 2001. Because Bangladesh is a Muslim country, no pigs were involved in the outbreak because pig husbandry was not conducted there. Each of these outbreaks is assumed to be a different spillover from the previous one. IEDCR and icddr,b found sporadic cases and 11 outbreaks of Nipah encephalitis from 2001 to 2011⁷⁴. Sentinel surveillance revealed three cases of NiV outbreaks. Nipah encephalitis epidemics occurred in 20 districts of Bangladesh, with 196 cases reported, and 150 (77 percent) of those infected died. For this condition, raw date juice consumption has been identified as the key risk factor⁷⁵. In 2004, the Centers for Disease Control and Prevention found that cases were four times more likely than controls to have consumed raw date palm sap and 7.3 times more likely to have been exposed to an outbreak of Nipah⁷⁶. Further investigation revealed that 21% of instances of Nipah linked to date juice consumption had not been misclassified⁷⁷.

6.3 India:

A direct transmission of NiV from bats to humans and from humans to bats was documented during India's first NiV outbreak in 2001 in Siliguri district of West Bengal, unlike the pandemic in Malaysia⁷⁸. In Kerala, a Nipah virus epidemic began in May 2018, 1800 kilometers distant from previous outbreak sites in East India in 2001 and 2007. This is the most recent information we have. Twenty-one of the affected people (16 of whom died and 18 of whom died) succumbed to the disease (laboratory confirmed). Researchers in Kerala identified indications of Nipah in fruit bats after conducting preliminary tests on bats (Megaderma spasm) (Teropas medius). In addition to his previous role as a guaranteed host in Bangladesh⁷⁹, P. Medias now fulfills same role in India. For the purpose of keeping track of Nipah virus in bats, we have evaluated and analyzed the published records of international Nipah virus surveillance data⁸⁰. For species in Asia, Australia, and Oceania, we used a feature-based machine learning strategy. At least four species of bats have been identified as having a relatively high probability of coming into contact with Nipah or Nipah, based on the similarity of characteristics with previously identified species that are Nipah virus-seropositive in Kerala⁸¹, in addition to the seven previously identified species. India's population is being infected with a virus in the same way. Researchers will need to do further research to determine how likely it is that the Nipah virus will spread across India. As long as there aren't any vaccinations or antivirals to combat Nipah encephalitis, the public's health is at risk⁸².

Table 1: Cases of Nipah virus infections across the world^83,84,85.

Country	Place	Year	Cases	Death Incidents
Malaysia		1998	283	109
Malaysia	Perak, Negeri Sembilan and Selangor	1999	265	105
Singapore	Singapore	1999	11	1
India	Siliguri	2001	66	50
Bangladesh	Meherpur	2001	13	9
Bangladesh	Naogaon	2003	12	8
Bangladesh	Manikganj and Rajbari	2004	42	14
Bangladesh	Faridpur	2004	36	27
Bangladesh	Tangail	2005	12	11
India	Nadia	2007	50	3-5
Bangladesh	Kushtia and Thakurgaon	2007	15	8
Bangladesh	Manikganj and Rajbari	2008	9	8
Bangladesh	Faridpur	2010	8	7
	Comilla, Dinajpur, Faridpur, Lalmohirhat, Nilphamari	2011	44	40
	Joypurhat	2012	12	10
	Gaibandha, Manikganj, Naogaon, Natore, Pabna	2013	24	21
Philippines		2014	17	9
Bangladesh		2015	261	199
		2017	3	2
India	Kerala	2018	21
India	Kozhikode and Malappuram	2018	18	17
Bangladesh		2019	8	7
		2020	6	4
		2021	2	0

7. CONCLUSION:

The pathogenesis and transmission of the Nipah virus have been greatly improved during the past two decades as a result of significant research. Understanding of this phenomenon will improve in the next decade. We must emphasize that this knowledge will be put to use in human clinical trials for Nipah viral vaccines and in the adjustment of risk variables to prevent infection. Developing procedures and medicines to treat infected people and reduce mortality and morbidity will be greatly aided by such knowledge. An important goal in agricultural and healthcare worker health care is preventing the spread of diseases like this. Even before outbreaks in Bangladesh and India, scientists from platforms like Global Outbreak Alert have shown that a network connecting veterinary and medical services is needed to communicate about this disease. Planned prevention methods can be specific and concrete if many sectors and a multidisciplinary approach are involved.

8. CONFLICT OF INTEREST:

There is no conflict of interest.

9. FUNDING:

No funding for this paper.

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Received on 29.10.2022 Modified on 24.12.2022

Research J. Pharm. and Tech 2023; 16(8):3588-3594.

DOI: 10.52711/0974-360X.2023.00592